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ESTABLISHMENT OF DNA TESTING SYSTEMS FOR THE DIAGNOSES OF GENETIC SUSCEPTIBILITY OF ATHEROSCLEROSIS AND THROMBOSIS

Research Project

Project/Area Number 11557206
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Laboratory medicine
Research InstitutionKeio University

Principal Investigator

WATANABE Kiyoaki  School of Medicine, Keio University, Professor, 医学部, 教授 (20101983)

Co-Investigator(Kenkyū-buntansha) TAKEI Izumi  School of Medicine, Keio University, Assistant Professor, 医学部, 講師 (80129519)
TANAHASHI Norio  School of Medicine, Keio University, Assistant Professor, 医学部, 講師 (10124950)
MURATA Mitsuru  School of Medicine, Keio University, Assistant Professor, 医学部, 講師 (50174305)
IWANAGA Shiro  School of Medicine, Keio University, Assistant Professor, 医学部, 助手 (70213303)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1999: ¥4,700,000 (Direct Cost: ¥4,700,000)
KeywordsATHEROSCLEROSIS / THROMBOSIS / GENETICS / POLYMORPHISM / GENETIC TESTING / RISK FEACTORS
Research Abstract

Genetic factors in combination with a number of environmental risk factors are involved in a predisposition to atherosclerosis and thrombosis. Coronary artery disease (CAD) and ischemic cerebrovascular disease (CVD) are typical human attributes that have a complex multifactorial etiology. The aim of the present study was to clarify the relationship between genetic polymorphisms found in factors relevant to thrombosis and disease phenotypes (i.e., sites of thrombus and severity of atherosclerosis), through a series of case-control studies involving patients with CAD, CVD, and deep vein thrombosis. We also aimed to establish systems to comprehensively evaluate the contribution of genetic factors to the pathogenesis of thrombosis in the Japanese populations, where allele frequencies are known to be quite different than Caucasians.
Polymorphisms in platelet GPIba receptor and coagulation factor XII were involved in susceptibility to CVD. We also found that polymorphisms in CETP and MTHFR we … More re associated with macroangiopathy in type 2 diabetes. In addition, factor XII polymorphism was associated with calcification of abdominal aorta in diabetic patients. Another novel finding of this study was the relationships between the activities or concentrations of certain factors (paraoxonase, homocystein, activated coagulation factor XII, ANP) and polymorphisms within each gene.
As previously shown in acquired factors, combinations of multiple genetic factors are believed to be crucial for the development of thrombotic disorders. We thus developed a new strategy to simultaneously analyze the genotypes of relevant polymorphisms. We also established methods to amplify relevant DNA fragments from whole blood in PCRs.
The ultimate goal of the clinical appreciation of polymorphic markers is to identify subgroups of individuals who are best prevented from developing diseases, or who respond best to dietary, behavioral, or pharmacologic interventions. For this purpose, polymorphisms need to be investigated not only in relation to disease susceptibility, but also with regard to responsiveness to treatment, and gene-environment interactions. Also, development of novel strategies to comprehensively assess the risk factors particular to the Japanese is warranted. Less

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Oguchi S, Ito D, Murata M, Yashida T, et al.: "Genoiyps distnbutaon of the 46C/T polymorphism of coagulatiou factor XII in the Japanese population : absence of its association with ischcmic cerebrovascuiar disease"Thromb Haemast. 83. 178-179 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matsubara Y, Hayakawa T, Tsuda T, Takeshita E, et al.: "Angiotensin convening enzyme insertion/deletion polymorphism is associated with plasma antigen levels of plasmanogen activator inhibitor-1 in healtby Japanese population"Blood Coagulation and Fibrinolysis. 11. 115-120 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sonoda A, Murata M, Ito D, Ohta A, et al.: "Association between platelet glycoprotein Ib α genotype and ischemic ccrebrovascular disease"Stroke. 31. 493-497 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ishil K, Oguchi S, Murata M, Mitsuyoshi Y, et al.: "Activated factor XII levels are depedent on factor XII 46C/T genotypes an factor XII zymogen levels, and are associated with vascular risk factors in patients and healthy subjects"Blood Coagulation and Fibrinolysis 11:115-120,2000. 11. 277-284 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ito D, Murata M, Watanabe K, Yashida T: "C242T polymorphism of NADPH oxidase p22 phox gene and ischemic cerebrovascular disease"Stroke. 31. 936-939 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Meguro S, Takei I, Murata M, Hirose H: "Cholesteryl ester tranffer protein polymorphism is associated with macroangiopathy in Japanese type 2 diabetes mellitus"Atheroscierosis. 156. 151-156 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Oguchi S., Ito D., Murata M., Yoshida T., et al.: "Genotype distribution of the 46C/T polymorphism of coagulation factor XII in the Japanese population: absence of its association with ischemic cerebrovascular disease"Thromb Haemost. 83. 178-179 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matsubara Y., Hayakawa T., Tsuda T., Takeshita E., et al.: "Angiotensin converting enzyme insertion/deletion polymorphism is associated with plasma antigen levels of plasminogen activator inhibitor-1 in healthy Japanese population"Blood Coagulation and Fibrinolysis. 11. 115-120 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sonoda A., Murata M., Ito D., Ohta A., et al.: "Association between platelet glycoprotein Ib α genotype and ischemic cerebrovascular disease"Stroke. 31. 493-497 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ishii K., Oguchi S., Murata M., Mitsuyoshi Y., et al.: "Activated factor XII levels are dependent on factor XII 46C/T genotypes and factor XII zymogen levels, and are associated with vascular risk factors in patients and healthy subjects"Blood Coagulation and Fibrinolysis. 11. 277-284 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ito D., Murata M., Watanabe K., Yoshida T. et al.: "Cholesteryl ester tranffer protein polymorphism is associated with macroangiopathy in Japanese type 2 diabetes mellitus"Stroke. 31. 936-939 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Meguro S., Takei I., Murata M., Hirose H., et al.: "Cholesteryl ester tranffer protein polymorphism is associated with macroangiopathy in Japanese type 2 diabetes mellitus"Atherosclerosis. 151. 151-156 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 太田敦美 ほか: "健康診断受診者および脳血管障害患者におけるANP遺伝子多型の比較と血中ANP濃度"臨床病理. (印刷中). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 村田満, 渡辺清明: "血小板無力症、BSS"遺伝子検査外注早わかり事典. 54-55 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 村田満, 伊東大介: "脳梗塞と遺伝子-遺伝的危険因子"Modern Medicine. 38. 364-369 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ito, D et al.: "Notch3 gene polymorphism and ischemic cerebrovascular disease"J. Neurol Neurosurg Psychat. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Megyro, S et al.: "Cholesteryl ester tranffer protein polymorphism is associated with macroangiopathy in Japanese type 2 diabetes mellitus"Atherosclerosis. 156(1). 151-156 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sonoda, A et al.: "Stroke and platelet glycoprotein Ib α polymorphisms"Thrombosis and Haemostasis. 85. 573-574 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ishii K, et al: "Activated factor XII levels are dependent on factor XII 46C/T genotypes and factor XII zymogen levels"Blood Congulation and Fibrinolysis. 11. 277-284 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sonoda A, et al: "Association between platelet glycoprotein Ib α genotype and ischemic cerebrovascular disease."Stroke. 31. 493-497 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Oguchi S, et al: "Genotype distribution of the 46C/T polymorphism of coagulation factor XII in the Japanese population"Thrombosis and Haemostasis. 83. 178-179 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sonoda A,Murata M,et al: "Association between platelet glycoprotein Ib α genotype and ischemic cerebrovascular disease"Stroke. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Oguchi S,Ito D,et al: "Genotype distribution of the 46C/T polymorphism of coagulation factor XII in the Japanese population"Thromb Haemost. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ishii K,Oguchi S,et al: "Activated factor XII levels are dependent on factor XII 46C/T genotypes and factor XII zymogen levels"Blood Coagulation and Fibrinolysis. (in press). (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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